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Sept. 12, 2019
00:01 On today's show. We speak to allergists, Dr. Payel Gupta about penicillin allergy. Dr Gupta is triple board certified in allergy and immunology, pediatrics and internal medicine and currently as a practice on the upper West side of Manhattan with ENT and allergy associates. My practice, although we're not in the same office, I'm out on long Island. We discuss how common penicillin allergy is and how commonly that diagnosis is actually incorrect and who should be gone for testing. She goes through the four types of hypersensitivity reactions and then focuses in on type one the IgE mediated reaction so we go through the presentation, the treatment and some commonly confused conditions. She teaches us how the testing is done, why we can trust it and then goes on to dispel some misconceptions about penicillin allergy. Dr Gupta earned her medical degree from Michigan state university and then pursued a residency in both medicine and pediatrics at rush university in Chicago. She then moved to New York city and completed a fellowship in allergy and immunology at SUNY downstate. She's currently on the board of the New York allergy and asthma society and serves as the treasurer and secretary. She's also a national spokesperson for the American lung association. She has her own podcast and you can find it @eachpodcast.com and you can follow her on Instagram at at NYC. Doctor,
01:19 Welcome to the physician's guide to doctoring a practical guide for practicing physicians, Dr. Bradley block interviews experts in and out of medicine to find out everything we should have been learning while we were memorizing Krebs cycle. The ideas expressed on this podcast are those of the interviewer and interviewee and do not represent those of their respective employers. And now here's Dr. Bradley Block.
01:49 Dr. Payel Gupta. Thanks so much for being on the show.
01:52 Thank you for having me.
01:54 So there was this review article that came out in the January, 2019 JAMA evaluation in management of penicillin allergy. And what it made me think is every single person that I encounter with a pendant cell analogy, I should be sending to an allergist to be tested. Is that true?
02:11 So yes, that article is great and there's something that I want to bring up before I answer your question. So essentially that article was talking about penicillin allergy and how penicillins are the most safest and most effective antibiotics that we really have, but that many patients are reporting allergies to these drugs. And in the U S we have 10% of people reporting a penicillin allergy and that number actually shoots up too 15% in patients that are older and patients who are hospitalized. So what does that mean? That means, and I mean essentially what we know is that although those many people are reporting an allergy, that the clinically significant IgE or T lymphocyte mediated penicillin allergy is actually uncommon. And so a lot of these self-reported allergies are not accurate. And the patient actually had a side effect of the penicillin or the other important point that they mentioned is that 90 to 95% of these patients are not allergic when we test them.
03:22 And we know that the IgE mediated penicillin allergy, actually Wayne's over time. And so that 80% of patients are becoming tolerant after a decade. So there's a lot of things to consider. And that's essentially what the article was trying to help make everyone aware of is that we can't just look at that penicillin allergy in the chart and just say, okay, avoid penicillin out antibiotics because you know that when we do that we are using more broad spectrum antibiotics and we're increasing the risk of Murcia and we're increasing the risk of vancomycin resistant and or caucus where using more broad spectrum antibiotics, which results in increase in C diff infections. And so this article is really just asking us to ask more questions and be critical thinkers and really see if the allergy has real blood. So I think after our discussion today, hopefully everyone will know a little bit more about penicillin allergy.
04:25 And so, well I'll be a little bit more informed and we might not need to send every single one of our patients who is reporting a penicillin allergy to an allergist. So some of the ways in which the patients will explain that to me is [inaudible]. Well, you know what, my mother had penicillin allergy, so I just tell everybody that I'm allergic and so that patients should definitely be sent to you for testing or you know, they've never had a reaction so they don't, this is really even need to go to testing or I don't even remember my, my parents usually the mother told me, my mother told me that I had a reaction as a kid and now I'm 45 so that patient should definitely go to you. But even someone who said, okay, I had a reaction, I got tested, I was found to be allergic.
05:12 But that was like 20 years ago. You've been that patient who was confirmed positive may have outgrown it. That patient should go to you as well, right? Is that correct? All of these patients. Hmm. That's a for me, I didn't actually have a reaction. Should go to you. You got it. That's it. That's exactly. It seems like a lot of people are going to need penicillin testing and that's gonna keep you allergists. Very busy. [inaudible] like that's a lot of testing we're talking about you. You told me before the show, like an interesting statistic about how many people are just going to need to be tested. Actually one of the statistics is that every allergist would be responsible for 6,000 people if we wanted to undiagnosed everyone. Okay. So that's like one penicillin allergy every day for 20 years. And then, but that's not even including all of the new allergies that are occurring over those in suing 20 years.
06:05 So wow. That is, that is a lot of testing. So if you're not sure, just send that person to be tested. Okay. So let's take a step back and talk about how, how does drug allergy present? Yeah, so that's a great starting point. So there's several different types of hypersensitivity reactions to drugs out there, but the most classic and the reaction that we're all worried about is anaphylaxis. And that's what we were mentioning is the IgE mediated reaction. And that's actually the type of hypersensitivity that we can test for in the office. So again, these reactions are immediate type hypersensitivity reactions or type one reactions. And then there's other types of reactions that people can have. Two drugs and those are called delayed onset hypersensitivity reactions. And there's types two through four delayed onset hypersensitivity reactions. So I'll quickly go through each of these and just talk about highlights.
07:05 So a classic IgE mediated allergy occurs within one hour of taking the medication. And what I thought was interesting is that at the time of onset is actually influenced by the route of administration. So if you have IB administration of antibiotic, then you can have the reaction within seconds to minutes while that same drug administered orally may cause some symptoms in three to 30 minutes if it's taken on an empty stomach or 10 to 60 minutes if it's taken with food. So those are things to remember. But again, it's all happening within that first hour. So it doesn't have to happen immediately all the time. But that hour is kind of like that he timeframe that you're looking for. And then you'll also want to see what medications the patient might be on because that time frame might change. For example, if the patient's on an anti-histamine, you might see that reaction and after an hour, okay, so when a patient, when we put a patient on an antibiotic, if they say that they developed a rash but it happened a few hours after administration of the drug, it makes it much, much less likely that this is really an IgE mediated drug allergy and it might be circumstantial.
08:18 We're going to get two different types of rashes to begin with. But I know from my patients I sometimes find it confusing and hard to tell when it's really a drug reaction or drug allergy and when it's not. I think this hour rule really works too. Help us differentiate could be from what is definitely not. So if it's well over an hour, it's very unlikely. This is a genuine IgE mediated drug allergy. Right. And again, you want to look and make sure that the patient isn't on an anti histamine because then it could be over an hour even if it is a true IgE mediated reaction. Does that make sense? Yes. Yeah. And then of course the symptoms are super important. So if it is an IgE mediated reaction, it's mediated by mass cells and basophils. And when they get activated they release histamine and other inflammatory mediators. And that's going to cause the hives, the difficulty breathing, wheezing, swelling of the eyes space and can ultimately lead type attention, which are all the classic symptoms of anaphylaxis.
09:24 Okay. So now we've, we've got the um, the muscles and the basophils in there. Yeah, stimulating this reaction. So sort of dropped. What's going to happen with the patient? [inaudible] manifestations, right. So I mean the manifestations, we mentioned the hives, difficulty breathing, wheezing, swelling of the eyes and face, and then ultimately hypotension. But so essentially, do you have any of those symptoms and combination and you're really worried about a true IgE mediated allergic reaction. And that's the type one. So then there's type two, which is one of the delayed onset reactions. And these are antibody mediated cell destruction reactions. So these appear five to eight days after exposure and can cause things like hemolytic anemia, thrombocytopenia, or neutropenia, since these are all the cells that are most often affected by the cell mediated destruction. So these are very uncommon. Type three is another form of an uncommon delayed onset hypersensitivity reaction.
10:29 And that's mediated by the IgG and the drug immune complex deposition and compliment activation. So all of that sounds confusing, but the most important things to remember is that this one essentially appears more in patients that aren't high dose or prolonged drug exposure. And they take one or two or more weeks to develop after drug exposure and [inaudible] take significant quantities of the antibody. And so that's why it takes longer or these antigen antibody complexes to develop. And so you'll see things like serum sickness, Eva rash, renal abnormalities, vasculitis, which typically presents as a palpable purpura or critique UI, fever. And in these patients you can have are to carry a [inaudible], but they'll have all of these other things, joint pains, lymphadnopothy, an elevated ESR and low complement levels. And then lastly, and I was getting kind of boring, you have the type or the delayed onset reaction, which is actually so type one and type four, the most common, and this isn't mediated by antibodies, but it's mediated, it's T cell mediated. And these reactions start about two to three days after taking the drug and basically because the T cells are involved, you're going to get a lot of skin findings. So this is Steven's Johnson's syndrome or TN toxic epidermal necrolysis and in this you're going to get rash, you're going to get Oh so joint pain sometimes and a lot of mucosal involvement. So you're going to get sloughing of the skin ulcerations and things like that.
12:12 Well I, I appreciate you keeping that brief for those, uh, those of the listeners who are commuting. That was definitely a flashback to step one and maybe step two and a good review definitely for any of the med students that are listening as well. So I, I appreciate that overview. So clearly covering all four of those types of reactions, that's going to be a lot. So we're going to keep today's discussion to the type one IgE mediated reaction and specifically focusing on on penicillin. So, so some of the trouble that I have is differentiating, you know, you mentioned hot, right? Yet. I have patients coming in with like a maculopapular rash on their chest and back and that sounds kind of like a drug allergy to me. Um, I, I sometimes have trouble, um, differentiating them. So first, can you focus in on what an IgE mediated rash looks like more specifically and then just what are some of the more commonly confused rashes and how we can tell them apart?
13:11 Yeah, so I think that you want to want to remember about highs is that they're going to be itchy. So if you don't have itching, it's most likely not hives. The second thing is, is that hives aren't going to be scarring. So you're going to have a patient that says, I have a weld on one arm and then 10 minutes later it's gone from that area without scarring and then it's on my neck. So those are some of the things that you want to remember about hives. And then other things can mimic hi like reactions. But if you have any kind of diffuse swelling of the skin and the maculopapular raised rash all over the body, that is not [inaudible] that that's not an urge to carry all rash and those rashes are usually not dangerous. But if you've got any kind of skin blistering or sloughing of the skin or obviously any signs of end organ damage like renal failure, anything like that, then we're looking at something totally different.
14:18 Alright, so, so let's say the patient presents with this maculopapular rash and they're calling me up right on the on call doctor over the weekend and w what do I tell them about taking that medication? Should I tell them to stop it? Should I tell them that they should continue with it? Should we switch it to something else of a, of a similar class or even the same class? How should I, how should I be managing that?
14:41 Yes. I would start by asking all those questions of [inaudible] are, are there any other worries, some signs like the blistering or sores in the mouth, any kind of other mucosal involvement you want to ask about those kinds of questions? If it doesn't sound like there's any other worrisome symptoms associated with the rash, then if you're the on call doctor, I would probably still have them stop the medication. If it ends up being something more severe, you want them to stop the medication. So I would say stop the medication and have them follow up with someone the next day if possible.
15:17 Well, what if you determine that it is a genuine IgE mediated reaction? Um, how are we going to treat that patient and how do we triage them to, okay, you can just take this medication over the phone versus you know, this is a patient that requires urgent management either, you know, going to urgent care for further assessment
15:39 the ER,
15:40 right? So first when you're treating a drug reaction, the first thing is you need them to stop the medication. That's the first thing. The second is that would these type one IgE media reactions anti-histamines are super important. So you want them to start [inaudible] an anti-histamine Benadryl is stronger than a laggers or tech or Claritin. So you want them to get a Benadryl or take whatever they have at home. But if they have Benadryl, that's the optimum. The other thing is is that obviously you know, you can have them start with that, but if there's any signs of breathing difficulties, hypotension, obviously any kind of dizziness, weaving, any of those things, they need to go, they need to call nine one one and go straight to the emergency rooms. But without any of those things, they can start [inaudible] the battery. Okay. At stop the medication and if they see any progression of the symptoms, then they need to go to the year.
16:36 Is there any role for a systemic steroid?
16:39 So some systemic steroids can help. They're not necessarily helping with that immediate reaction, but they can help with any kind of delete and inflammation reactions. So most people do get at least one dose of oral steroids when they're treating pretty severe reaction.
16:55 All right. So you have a patient who you think either you think might've had a drug allergies since they're describing what you just described or they come in with this remote history of, no, my mother said when I was two I got a rash to penicillin and now I'm 55 so how do you test for that and do those patients who one gives a remote vague history and one gives a very concise recent history. Is the testing any different for those patients?
17:25 No, the testing isn't any different. It's really just we're, you know, again we're testing for patients for the IgE mediated type one hypersensitivity reactions and we can't test patients for those other forms of delayed reactions. So the practical things to remember for these patients, for referring doctors, like the ones that are listening is that number one, not allergists will perform the testing on the same day as the first consult visit. So you should have the patient call the office to see if they're going to have a consult first and then testing or if the testing is going to be performed on the same day. So if it's possible that the testing could be performed on that same day as the visit, then you need to make sure that the patient is off of any kind of anti-histamine for at least three to five days. So this also depends on the allergist, on how long they want the patient to be off of anti-histamine.
18:22 And so I would have them call the office that you're referring them to and make sure that they understand exactly how long that physician wants them off of their anti-histamines or any other medications that the doctor feels might interfere with the testing. Most people just believe it's anti-histamines, but other physicians have a list of medications that they usually want the patient to avoid. And then the other thing is that the testing is really similar to what we do for environmental allergy testing in the office. So it just involves a skin prick test with a positive and negative control and two different penicillin reagents called free pen Kenji. So one important thing to remember is that most penicillin allergic patients aren't allergic to the actual intact penicillin molecule. So most of them are allergic to degradation products of the penicillin. And so that's why we have to use these special reagents and we can't just use whatever medication they were on. We need to use these special reagents called pre penname. Kenji, okay.
19:28 Correct me if I'm wrong, but penicillin is the only standardized drug that you can test like that, that that comes with like a standardized kit. Anything else? Like if a patient says they're allergic to a Zithromycin there, there's no kit that you can order for standardized days with remixing you gotta kinda Jerry rig a test.
19:48 Exactly, exactly. And that's why [inaudible] the testing for those other medications isn't always as accurate as it is for penicillins because we're [inaudible] yeah, doing that. Jerry rigging.
19:59 Okay, so sorry. So you've got the two forms of penicillin and then how do you administer those?
20:04 So you're going to do a skin prick test. So it's just literally pricking the top layer of the skin and waiting for that mass cell degranulation if the patient is truly allergic and so if they are allergic, they're going to get a little mosquito bite type reaction on their skin. And again, we always do a positive and negative control so that if patients for whatever reason have really sensitive skin and their negative control has a reaction and we can [inaudible] look at the negative control compared to what we're getting and see if it looks like a true app reaction or if it's just that the patient has super sensitive skin and reacts to just that fricking sensation. If that skin prick test is negative, then we moved to an intradermal test, which is essentially a deeper, a PPD type tests where we take those same reagents and we put them in a little bit deeper and we wait for another 20 minutes.
21:02 And if that's negative then we can move on to what we call an oral challenge. All right. And then I would imagine you after the oral challenge, cause you're what you described about the hour, a patient's got to sit there in the waiting room for an hour to see if they react. Right, exactly. So what we do with the oral challenge, we give them a dose of a medication that would be appropriate for their age, their height, their weight, all that kind of stuff and give them that dose. And then we had them wait for an hour, make sure that they don't have that immediate reaction. And just to swing back a little bit and negative predictive value for penicillin test, that's negative approaches 100% when we combine it when uh, oral challenge. So that's pretty awesome. So if that patient is negative, we're not too worried that they're going to have her another reaction.
21:56 Okay. So put it another way. If the testing is negative, there is no reason to doubt it. Once the patient has negative testing for penicillin, they are not allergic to penicillin. Period. End of sentence. Possibly mic drop. Right? So I mean again, that's, which is 95% with just the skin prick. And then approach it as I was getting pregnant into dremmel and then approaches 100% when you do that, we're all challenged. And then the only caveat to that is that if a patient gets resensitize at some point, there are just like the general population, they have a one to 3% chance. Okay. Having a penicillin allergy down the line so you could still become allergic to a name. And so just like if you become sensitized to it, it doesn't necessarily last for the rest of your life if you're found to be negative, that doesn't necessarily last for the rest of your life.
22:46 So no, no, no. I don't have penicillin allergy. I was tested for it. And as your lips are blowing up and you're starting to wheeze, that might be a genuine IgE mediated, a penicillin allergy. Right. Essentially you're going out there like the rest of everyone else. Yeah, just like the general population. Got it. Okay. But once again, just to reiterate, if the testing is negative, you do not have a penicillin allergy. Right. Got it. Okay. So, so aside from not necessarily trusting that negative as we should, are there any other misconceptions about either penicillin allergy testing, drug allergies in general that you've liked, that you'd like to miss dispel while you're on the podcast? Yeah, I think some of the big ones are in tolerance and side effects. [inaudible] different than a true allergic reaction. So things like diarrhea or a yeast infections or headaches or nausea or vomiting or fatigue, those aren't allergic reactions. They, they might be side effects. They might be intolerances, but they're not true. IgE mediated reactions because we already talked about all of those symptoms. So you might want to put it in the chart, but you don't want to put it in a chart as an allergy. You might want to say this patient didn't tolerate this particular form. They didn't tolerate amoxicillin, but that doesn't mean you can't use another medication in that same class.
24:15 I dunno if the EMR has a, has a spot for that. That might be challenging for some people. You might have to just leave it off and let the patient, you know when you're trying to prescribe them. When the next time they get prescribed something, just let them voice that upsets their stomach or gives them a headache rather than risks putting it under allergy. You know, we, we don't necessarily, not all EMR I think have that section. So I would, I would warn against, well you know, over documenting something like that.
24:42 Yeah, I mean you can put it if you have a general notes section or whatever for your, for the next two, for your, yeah. For yourself. For yourself. Exactly. And then other things, IgE, penicillin, allergy doesn't run in families. So if you have a relative with a penicillin allergy, that doesn't mean that you have a penicillin allergy. Things like Steven Johnson syndrome and dress the type four hypersensitivity reactions, those might have a genetic component, but we don't really know exactly what that is. And even in those situations, the patient can still have the medication even if they had that family history. And so you, you still don't want to avoid it. And then we kind of mentioned this before, but I think the biggest problem is is that once you put something in the chart, everyone thinks it's permanent. It's just not there. You might grow out of the penicillin allergy and you just want to keep editing that list over time and just making sure that that the list is accurate.
25:42 All right, well that was extremely informative and I can see it in your near future that you are going to have a large influx of penicillin testing to do. I hope that's part of your practice that you enjoy because your 6,000 patients is per allergists. That's, that's quite a few to to have the test to get rid of the public health problem that's become penicillin allergy. So you actually have your own podcast, the itch. Can you, can you tell us about your podcast work? People can find it and what it's all about?
26:13 Yeah, so it's a, it's called the itch as you mentioned, and it's about allergies, food allergies, environmental allergies, asthma, other immune deficiency disorders with [inaudible], a woman named Courtney and she's an allergy blogger and so she personally has a lot of food allergies and eczema and asthma. And so we basically just break down all opens for patients. And actually I think it's great for medical students to, if they're starting a rotation, an allergy just because we kind of talk about everything and answer all of the burning questions that Courtney might have. Can we also interview people who are doing cool things in the allergy space? So it's a fun podcast and yeah, you can find us on [inaudible] at the itch podcasts and our website is [inaudible], it's podcast.com. Hopefully I'll check it out.
27:05 Yeah, I think that that would be great for anyone who's either you're a general practitioner and you're treating patients with allergies, a great way for them to learn more about it. Cause if you have, if you're foil on the show is a, you know, someone from the lay public. Yeah. It's going to keep you a little more, a little, a little less technical so that, so that it's really open for everybody to understand. Yeah, I think that's, that's a great concept. I've certainly learned a lot from the episodes that I've listened to. I think it's very, very engaging and uh, it's a great public service as well for all of those patients that to give them a better idea of what's going on. Cause I've found, you know, a lot of my patients that have asthma undertreated or allergies are undertreated or allergies being over-treated. Everyone seems to think everything's out related to allergies. People were coming in with sinus headaches and, and uh, and were actually migraines. But what are they taking? They're taking Claritin. So there's a bunch of, um, misinformation out there and I really to use a term that our practice likes to use, kudos to you for, uh, for great patient facing podcasts you've got there. Thank you. Thank you. Well, thanks a lot for taking the time to dispel some myths and educate us about penicillin allergy and IgE mediated drug reactions. It has been a pleasure.
28:17 Thank you.
28:22 That was Dr. Bradley block at the physician's guide to doctoring. He can be found at physician's guide to dr [inaudible] dot com or wherever you get your podcasts. If you have a question for a previous guest or have an idea for a future episode, send a comment on the webpage. Also, please be sure to leave a five star review on your preferred podcast platform. We'll see you next time on the physician's guide to [inaudible].
28:58 Today's guest is not an attorney, accountant or financial advisor, and neither am I. This information should not be considered personalized financial advice and we will not be held liable for the use of any information contained within this interview. It is your responsibility to verify anything you've heard using other trusted and reputable resources.